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Up-Frameshift Suppressor 3 作为一种预后生物标志物与免疫浸润相关:泛癌分析。

Up-Frameshift Suppressor 3 as a prognostic biomarker and correlated with immune infiltrates: A pan-cancer analysis.

机构信息

Department of General Surgery, Shijiazhuang People's Hospital, Shijiazhuang, P. R. China.

Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, P. R. China.

出版信息

PLoS One. 2022 Oct 4;17(10):e0273163. doi: 10.1371/journal.pone.0273163. eCollection 2022.

Abstract

BACKGROUND

The mRNA expression of protein Up-Frameshift Suppressor 3 Homolog B (UPF3B) differ in different tumors. However, the clinical relevance of UPF3B in cancer patients, such as with prognosis, tumor stage, and levels of tumor-infiltrating immune cells remain unclear.

METHODS

We performed bioinformatics analysis of UPF3B with The Cancer Genome Atlas (TCGA) database (https://xenabrowser.net) and TIMER2.0 (Tumor Immune Estimation Resource 2.0, http://timer.comp-genomics.org/). UPF3B expression in 33 cancers versus counterpart normal tissues was analyzed using TCGA pan-cancer data. The influence of UPF3B in long-term prognosis was evaluated using Kaplan-Meier method, and the associations between UPF3B transcription levels and immune-related gene expression, immune cell infiltration, tumor microenvironment (TME) score are analyzed by spearman correlation analysis. Enrichment analysis of UPF3B was conducted using the R package "clusterProfiler."

RESULTS

The transcriptional level of UPF3B was dysregulated in the human pan-cancer dataset. A significant correlation was found between the expression of UPF3B and the pathological stage of Esophageal Carcinoma (ESCA), Kidney Chromophobe (KIHC), Liver Hepatocellular Carcinoma (LIHC), and Skin Cutaneous Melanoma (SKCM). Multiple cancer types with high transcriptional levels of UPF3B were associated with a significantly worse prognosis. The functions of expressed UPF3B gene are primarily related to ubiquitin mediated proteolysis, cell cycle, and mRNA surveillance pathway. Our results also show that immune cells infiltration and immunosuppressive markers such as CTLA-4, PD-1 and PD-L1 significantly correlate with UPF3B expression.

CONCLUSIONS

In the present study, we synthetically explored the expression status and prognostic significance of UPF3B, and the relationship with clinic characters and immune microenvironment across cancers. Our results may provide novel insights for UPF3B as an immunotherapeutic target and valuable prognostic biomarker in various malignant tumor.

摘要

背景

蛋白 Up-Frameshift Suppressor 3 同源物 B(UPF3B)的 mRNA 表达在不同肿瘤中存在差异。然而,UPF3B 在癌症患者中的临床相关性,如预后、肿瘤分期和肿瘤浸润免疫细胞水平仍不清楚。

方法

我们使用 The Cancer Genome Atlas(TCGA)数据库(https://xenabrowser.net)和 TIMER2.0(肿瘤免疫估计资源 2.0,http://timer.comp-genomics.org/)进行 UPF3B 的生物信息学分析。使用 TCGA 泛癌数据分析 33 种癌症与对应正常组织中 UPF3B 的表达。使用 Kaplan-Meier 方法评估 UPF3B 对长期预后的影响,并通过 Spearman 相关分析分析 UPF3B 转录水平与免疫相关基因表达、免疫细胞浸润、肿瘤微环境(TME)评分之间的关系。使用 R 包“clusterProfiler”对 UPF3B 进行富集分析。

结果

UPF3B 的转录水平在人类泛癌数据集中原发性失调。UPF3B 的表达与食管鳞癌(ESCA)、肾嫌色细胞癌(KIHC)、肝肝细胞癌(LIHC)和皮肤黑色素瘤(SKCM)的病理分期显著相关。多个 UPF3B 转录水平较高的癌症类型与预后显著较差相关。表达的 UPF3B 基因的功能主要与泛素介导的蛋白水解、细胞周期和 mRNA 监测途径有关。我们的结果还表明,免疫细胞浸润和免疫抑制标志物如 CTLA-4、PD-1 和 PD-L1 与 UPF3B 表达显著相关。

结论

在本研究中,我们综合探讨了 UPF3B 在各种恶性肿瘤中的表达状态和预后意义,以及与临床特征和免疫微环境的关系。我们的结果可能为 UPF3B 作为免疫治疗靶点和各种恶性肿瘤有价值的预后生物标志物提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dba4/9531787/b42f7e5b09f6/pone.0273163.g001.jpg

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